Showing papers by "Suzanne Oparil published in 2000"
TL;DR: This review of current concepts regarding the definition, etiology, and treatment of essential hypertension is intended to aid the clinician in identifying those individuals at high risk who need to undergo evaluation and treatment, as well as in selecting optimal treatment strategies for hypertensive patients with comorbid conditions and/or target organ damage.
Abstract: Essential hypertension remains a major modifiable risk factor for cardiovascular disease (CVD) despite important advances in our understanding of its pathophysiology and the availability of effective treatment strategies. High blood pressure (BP) increases the risk of CVD for millions of people worldwide, and there is evidence that the problem is only getting worse. In the past decade, age-adjusted rates of stroke incidence have risen, and the slope of the age-adjusted rate of decline in coronary disease has leveled off. The incidence of end-stage renal disease and the prevalence of heart failure have also increased. A major contributor to these trends is inadequate control of BP in the hypertensive population. This review of current concepts regarding the definition, etiology, and treatment of essential hypertension is intended to aid the clinician in identifying those individuals at high risk who need to undergo evaluation and treatment, as well as in selecting optimal treatment strategies for hypertensive patients with comorbid conditions and/or target organ damage. The part of the review that deals with the genetic basis of hypertension and the gene/environment interaction that may lead to elevated BP is still a work in progress. Information gained from the Human Genome Project and from ongoing studies of the genetic basis of hypertension both in animal models and human populations may revolutionize the treatment of hypertension by replacing current empirical therapy with more effective, targeted treatments based on the genotype of the patient. Concepts introduced in this review form the basis for such “pharmacogenomic” approaches to antihypertensive therapy.
BP is a quantitative trait that is highly variable1 ; in population studies, BP has a normal distribution that is slightly skewed to the right. There is a strong positive and continuous correlation between BP and the risk of CVD (stroke, myocardial infarction, heart failure), renal disease, …
1,092 citations
TL;DR: These observations provide direct demonstration of adventitial fibroblast migration into neointima of arteries after endoluminal injury.
Abstract: Background—Clinical and experimental evidence suggest that the adventitia participates in the response to endoluminal vascular injury. The current study used a direct approach to test the hypothesis that, after balloon injury of the rat carotid artery, adventitial fibroblasts migrate in a luminal direction and contribute to neointima formation. Methods and Results—Primary syngeneic adventitial fibroblasts were stably transduced with retroviral particles coordinating expression of β-galactosidase (LacZ) and introduced into the adventitia of right carotid arteries of rats immediately after balloon injury. At defined times after injury and fibroblast implantation, rats were euthanized, and arterial tissue was examined for detection of LacZ mRNA (reverse transcription polymerase chain reaction), DNA (polymerase chain reaction), and in situ enzymatic activity. LacZ expression was detected in the media 5 days postinjury and in both media and neointima at 7, 10, and 14 days postinjury. LacZ was undetectable in i...
269 citations
TL;DR: Older adults can successfully increase milk intake, thereby meaningfully improving their nutrient intakes and Dietitians can play a key role in disseminating this advice.
Abstract: Objective To assess the impact of increased consumption of milk, without other dietary advice, on older adults' energy and nutrient intakes, weight, cardiovascular risk factors (blood pressure, plasma lipid levels), and quality of life Subjects/setting Two hundred four healthy men and women, aged 55 to 85 years, who consumed fewer than 15 dairy servings per day were chosen from six US academic health centers Design Randomized, controlled open trial Intervention Advice to increase skim or 1% milk intake by 3 cups per day (n=101) or to maintain usual diet (n=103) for 12 weeks after a 4-week baseline period Main outcome measures Changes in energy and nutrient intake assessed from 3-day food records, body weight, blood pressure, and plasma lipid levels Statistical analyses performed Group-by-time analysis of variance with repeated-measures, χ 2 test Results Compliance with the intervention was good Compared with controls, participants in the milk-supplemented group significantly increased energy, protein, cholesterol, vitamins A, D, and B-12, riboflavin, pantothen ate, calcium, phosphorus, magnesium, zinc, and potassium intakes Prevalence of nutrient inadequacy, assessed for nutrients with Estimated Average Requirements, decreased among women in the milk group for magnesium (40% at baseline vs 13% at 12 weeks, P P P P P =002) Quality of life scores were high at baseline and remained high throughout Applications/conclusions Older adults can successfully increase milk intake, thereby meaningfully improving their nutrient intakes Dietitians can play a key role in disseminating this advice J Am Diet Assoc 2000; 100:810-817
211 citations
TL;DR: Combined therapy with a calcium antagonist and an ACE inhibitor provides blood pressure control equal to that of high-dose calcium antagonist monotherapy but with significantly fewer dose-dependent adverse experiences such as vasodilatory edema.
Abstract: The present 2 multicenter studies were designed to evaluate whether patients with essential hypertension derived equal benefits from use of combination therapy with a calcium antagonist and angiotensin-converting enzyme (ACE) inhibitor as from doubling the dose of the calcium antagonist. After a 2-week washout and a 2-week single-blind placebo run-in period, a total of 1,390 patients were treated with either nifedipine 30 mg (study 1) or amlodipine 5 mg (study 2) once daily for 4 weeks. The 1,079 patients whose diastolic blood pressure remained between 95 and 115 mm Hg were randomized to 8 weeks of double-blind therapy with amlodipine 5 mg/benazepril 10 mg, amlodipine 5 mg/ benazepril 20 mg, nifedipine 30 mg or nifedipine 60 mg (study 1), and amlodipine 5 mg/benazepril 10 mg, amlodipine 5 mg/benazepril 20 mg, amlodipine 5 mg or amlodipine 10 mg (study 2). Both doses of the calcium antagonist/ACE inhibitor combination therapy lowered diastolic pressure as much as the high dose and significantly better than the lower dose of calcium antagonist monotherapy (with either nifedipine or amlodipine). However, 15% of patients in the nifedipine high-dose monotherapy group and 24% in the amlodipine high-dose monotherapy group presented with some form of edema. In contrast, the incidence of edema was similar for patients treated with both combination therapy and low-dose calcium antagonists. Thus, combination therapy with a calcium antagonist and an ACE inhibitor provides blood pressure control equal to that of high-dose calcium antagonist monotherapy but with significantly fewer dose-dependent adverse experiences such as vasodilatory edema. Inc.
125 citations
TL;DR: Results indicate that the vasoprotective effect of E2 in the balloon-injured rat carotid artery model is mediated by ER.
Abstract: Background—Previous studies have shown that estrogen (E2) is vasoprotective in multiple animal models of vascular injury, including mice with homologous disruptions of either the α or β isoforms of the estrogen receptor (ER) gene, calling into question the ER dependency of the vasoprotective effect. This study used ICI 182,780, a nonselective ER antagonist, to test the hypothesis that the vasoprotective effect of E2 in the rat carotid injury model is ER mediated. Methods and Results—Intact female Sprague-Dawley rats were divided into 4 groups and treated with the nonselective ER antagonist ICI 182,780 (ICI; 0.5, 1.5, or 5 mg · kg−1 · d−1, subcutaneously [S.C.]) or vehicle, beginning before balloon injury of the right common carotid artery and continuing for 14 days afterward. Four groups of ovariectomized rats (OVX) were treated with 17β estradiol (E2) (20 μg · kg−1 · d−1, S.C.) alone or combined with ICI 5 mg · kg−1 · d−1, S.C.; with ICI 5 mg · kg−1 · d−1 alone; or with vehicle according to a similar pro...
121 citations
TL;DR: The hypothesis that endogenous ET-1 plays a major role in hypoxic pulmonary vasoconstriction/hypertension, right heart hypertrophy, and pulmonary vascular remodeling is supported and ET-receptor blockers may be useful in the treatment and prevention of hypoxia-induced pulmonary hypertension in humans.
Abstract: Biochemical and molecular biological evidence indicates that endothelin (ET)-1 and its receptors are selectively upregulated in the lung during exposure to hypoxia, while functional evidence indicates that ET-1 is a major mediator of hypoxia-induced pulmonary vasoconstriction and vascular remodeling. Hypoxia stimulates ET-1 gene transcription and peptide synthesis in cultured endothelial cells, and plasma ET-1 levels are increased in patients with primary pulmonary hypertension, and in humans exposed to high altitude, while immunoreactive ET-1 and ET-1 mRNA levels are increased in pulmonary artery endothelial cells of patients with primary pulmonary hypertension. Rats exposed to normobaric hypoxia exhibit increased pulmonary artery pressure, increased ET-1 peptide levels in plasma and lung, and selective increases in steady-state ET-1 and ET(A) and ET(B) receptor mRNA levels in lung but not in organs perfused by the systemic vasculature. The observations that both ET-1 and its major vascular smooth-muscle cell receptor are upregulated in response to hypoxia suggest that ET-1 may be a mediator of hypoxia-induced pulmonary hypertension. Moreover, hypoxic pulmonary vasoconstriction and vascular remodeling can be prevented and reversed by administration of either an ET(A)-selective or a combined ET(A) and ET(B) receptor antagonist. These findings support the hypothesis that endogenous ET-1 plays a major role in hypoxic pulmonary vasoconstriction/hypertension, right heart hypertrophy, and pulmonary vascular remodeling and suggest that ET-receptor blockers may be useful in the treatment and prevention of hypoxic pulmonary hypertension in humans.
87 citations
TL;DR: Overall, gender specific differences in the pathogenesis and response to treatment of hypertension exist, and must be taken into consideration.
Abstract: Cardiovascular disease remains the most common cause of death in women worldwide, with hypertension being the most common modifiable risk factor for cardiovascular disease in both sexes. Further, obesity plays a critical role in the development and management of hypertension with a disproportionate effect on minority women. Overall, gender specific differences in the pathogenesis and response to treatment of hypertension exist, and must be taken into consideration.
83 citations
TL;DR: It remains to be determined, however, whether the observed pharmacologic and pharmacokinetic differences among the members of the ARB class will have a clinically significant impact on long-term cardiovascular outcomes and reductions of cardiovascular mortality.
79 citations
Book•
01 Jan 2000
TL;DR: A history of Clinical Hypertension from 1827-1970 and current Prescribing Practices, as well as new Interpretations of Blood Pressure: Importance of Pulse Pressure, show the need to consider evidence-based medicine.
Abstract: I. Background and Historical Aspects: A History of Clinical Hypertension from 1827-1970. Epidemiology of Hypertension. II. Pathophysiology:Pathophysiology of Hypertension. Genetics. Sympathetic Nervous System. Environmental and Psychosocial Stress in Hypertension Onset & Progression. Renin and Prorenin. Angiotensinogen. Angiotensin Converting Enzyme: Basic Properties, Distribution and Functional Role. The AT1 and AT2 Angiotensin. Prognostic Implications of Renin Status. Metabolic Abnormalities in Hypertension. Obesity Related Hypertension as a Metabolic Disorder. Primary Arterial Pathology. Arterial Stiffness. Endothelin. Nitric Oxide in Hypertension. Natriuretic Peptides. Eicosanoids. Calcitonin Gene-Related Peptide and Hypertension. Kallikrein-Kinin System. Diet-Nutrition. Diet-Micronutrients. Obesity Hypertension: Effects on the Cardiovascular and Renal Systems in the Therapeutic Approach. Alcohol and Hypertension. III. Target Organ Damage/ Cardiovascular Complications: Total Risk. New Interpretations of Blood Pressure: Importance of Pulse Pressure. Coronary Atherosclerotic Sequelae of Hypertension. LVH-CHF. Stroke and Hypertension. End Stage Renal Disease. IV. Diagnosis: Initial Evaluation and Follow-up. Measurement Issues. White Coat Hypertension. V. Treatment General Considerations: Evidence-based Medicine. Outcomes in Treating Hypertension. Benefits of Treating Hypertension: Lessons From Clinical Trials. Ongoing Clinical Trials: An Overview. Antihypertensive and Lipid Lowering to Prevent Heart Attack Trial. LIFE. Changing Approaches to Diagnosis and Treatment of Hypertension (JNC 6). Critical Assessment of Hypertension Guidelines. Current Prescribing Practices. The Calcium Channel Blocker Controversy. Justifications for Treating Mild Hypertension (Surrogate Endpoints). Cost Effectiveness of Antihypertensive Therapy in a Managed Care Setting. Nurse Clinics. Community Outreach. Medication Compliance. for Antihypertensive Therapy. VI. Life Style Modification: Diet Micronutrients/Special Foods. Diet
79 citations
TL;DR: Criteria for initiation of treatment now take into consideration total cardiovascular risk rather than BP alone, such that treatment is now recommended for persons whose BP is in the normal range but still bear a heavy burden of CVD risk factors or established CVD.
Abstract: The goal of antihypertensive treatment is to reduce overall CVD risk and thus its morbidity and mortality rates. In any given patient, the decision to begin treatment is governed by the risk of CVD, which is determined by the magnitude of the BP elevation and the presence or absence of target organ disease and/or additional CVD risk factors. Recent consensus committees, including JNC VI and the World Health Organization–International Society of Hypertension (WHO-ISH) Guidelines Subcommittee, have modified traditional treatment recommendations in several important ways3,35 : (1) Criteria for initiation of treatment now take into consideration total cardiovascular risk rather than BP alone, such that treatment is now recommended for persons whose BP is in the normal range but still bear a heavy burden of CVD risk factors or established CVD. (2) Systolic BP is recognized as an important target for treatment, particularly in older persons, because it is an even more important determinant of CVD risk than diastolic BP. (3) More aggressive BP goals are recommended for hypertensive patients with comorbid conditions such as diabetes mellitus or renal insufficiency. (4) The importance of tailoring the choice of antihypertensive drug treatment to the patient’s individual profile of concomitant CVD risk factors/comorbid conditions is emphasized. (5) The role of simultaneous reduction of multiple CVD risk factors in improving prognosis in hypertensive patients is stressed. (6) Home and ambulatory BP measurement has been recommended because of its value in guiding therapy and enhancing adherence to treatment. (7) Greater reliance on evidence-based medicine (ie, results of randomized controlled trials with CVD outcomes) in making treatment decisions has been endorsed.
JNC VI has arrived at an empirical classification that stratifies hypertensive patients into risk groups for therapeutic decisions (Table 4⇓). Risk group A includes patients who do not have clinical CVD, target …
74 citations
TL;DR: The following review summarizes the present knowledge of the role of EDCF and EDRF in such processes with major focus on pulmonary endothelial dysfunction in hypoxia-induced pulmonary hypertension.
TL;DR: It is concluded that the ability of diet to lower BP successfully may result from the additive contributions of multiple components, perhaps by virtue of their suppressive effects on circulating vasoactive calcium regulating hormones.
TL;DR: The successful lowering of blood pressure during 12 months of follow-up in a large cohort of patients with hypertension and LVH on ECG is demonstrated, but the need for two or more drugs to control high blood pressure in most of these patients is emphasized.
TL;DR: It is suggested that estrogen indirectly attenuates integrin-beta(3)-dependent adventitial fibroblast migration after inhibition of OPN expression in activated VSMCs.
Abstract: Background—Previous in vitro studies have suggested that estrogen attenuates the vascular injury response by modulating vascular smooth muscle cell (VSMC) expression of soluble factor(s) directing migration of adventitial fibroblasts. Previous in vivo studies have established a role for osteopontin (OPN) and its integrin receptors after vascular injury. In this study, we examined OPN expression in activated VSMCs, its modulation by estrogen, and its effects on adventitial fibroblast migration. In addition, the relative functional roles of β1- and β3-integrin–matrix interactions were examined. Methods and Results—Primary cultures of VSMCs and adventitial fibroblasts were derived from female Sprague-Dawley rats. Serum-activated VSMCs expressed high levels of OPN mRNA and secreted protein that was effectively inhibited by estrogen treatment (10−7 mol/L). Compared with VSMCs, fibroblasts expressed similar levels of integrins αν and β1 and higher levels of integrin-β3. Exogenous OPN (5.0 to 40 μg/mL) directed ...
TL;DR: L'etude Syst-Eur (Systolic Hypertension in Europe) a ete interrompue prematurement car une reduction significative du nombre d'accidents vasculaires cerebraux and d'evenements cardiaques (fatals et non-fatals) a Ete observee chez les patients traites par the nitrendipine par rapport au placebo.
Abstract: Les inhibiteurs calciques ont clairement demontre leur efficacite dans la reduction de l'hypertension avec des effets secondaires moderes. Toutefois, il existe moins de donnees concernant leur effet sur la mortalite et les evenements cardiovasculaires. Le risque de mortalite est plus eleve avec les molecules a courte duree d'action et l'on s'interroge toujours pour savoir s'il s'agit d'un effet specifique a cette classe de medicaments ou d'un effet propre aux produits a liberation rapide par rapport a ceux a liberation prolongee. Plusieurs etudes prospectives a grande echelle ont etudie ou etudient actuellement les effets des inhibiteurs calciques a duree d'action prolongee sur la morbimortalite chez les sujets hypertendus. L'etude Syst-Eur (Systolic Hypertension in Europe) a ete interrompue prematurement car une reduction significative du nombre d'accidents vasculaires cerebraux et d'evenements cardiaques (fatals et non-fatals) a ete observee chez les patients traites par la nitrendipine par rapport au placebo. Six autres etudes, portant sur plus de 90 000 patients presentant des profils de risque cardiovasculaire divers, comparent actuellement l'effet des inhibiteurs calciques a longue duree d'action avec celui des traitements antihypertenseurs classiques. Les resultats de ces etudes permettront de mieux guider les traitements afin de reduire l'atteinte des organes cibles et la morbimortalite liees a l'hypertension.
TL;DR: The findings suggest that the increasing use of antihypertensive medication may in part explain the major decline in mortality from cardiovascular disease observed in the United States since the late 1960s.
Abstract: The classic outcome trials in hypertension, most of which used diuretics and b-blocking agents as first-line antihypertensive agents, have shown that antihypertensive drug treatment greatly reduces the risk of stroke, heart failure, and left ventricular hypertrophy (LVH) However, it is less successful in preventing fatal and nonfatal coronary heart disease (CHD) [1] In the Framingham Heart Study, increased rates of use of antihypertensive medications, from 23% to 246% among men and from 57% to 277% among women, were associated with reduced prevalence of hypertension (blood pressure [BP]>160/100 mm Hg) Reductions were from 185% to 92% among men and from 280% to 77% among women The prevalence of electrocardiographic evidence of LVH, an index of target organ damage, was reduced from 45% to 25% among men and from 36% to 11% among women These findings suggest that the increasing use of antihypertensive medication may in part explain the major decline in mortality from cardiovascular disease observed in the United States since the late 1960s Yet, despite these effective treatments, many important questions remain, some of which have been addressed by recently completed and ongoing clinical trials: • Are the newer classes of drugs, such as the calciumchannel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin-II type-1 receptor blockers (ARBs), or a-adrenergic blockers (ABs) superior to diuretics or b-blockers in preventing cardiovascular disease and events? • Do specific classes of antihypertensive drugs, over and above their blood pressure–lowering effects, benefit specific subgroups of hypertensive patients? • What is the appropriate BP goal in various patient groups? • Are specific antihypertensive drugs indicated in special groups of patients, such as the very elderly (>80 years), normotensive persons at high cardiovascular risk, patients with type 2 diabetes, patients with stage 1 hypertension, or hypertensive patients of African-American extraction?
01 Jan 2000
TL;DR: In this chapter, vasoprotective actions of estrogen exerted at the level of the arterial wall will be considered in the context of balloon injury models and hypercholesterolemia.
Abstract: Gender plays an important role in the modulation of cardiovascular risk and events. Cardiovascular disease is less prevalent in premenopausal women than it is in age-matched men, but there is an increase in coronary risk and events in women after menopause (1). Although a prominent antiatherogenic response to estrogen is a reduction in plasma low density lipoprotein cholesterol (LDL-c) and an elevation of high density lipoprotein cholesterol (HDLc), other benefits are achieved by processes that are independent of changes in plasma lipid profiles (2–4). In this respect, estrogen therapy has proven to be effective in blunting the vascular injury response via both genomic and nongenomic mechanisms (5). Balloon injury of the rat carotid artery is an experimental paradigm that is commonly used to study mechanisms of atherogenesis. Estrogen minimizes the vascular injury response in this model through both direct antiproliferative effects and indirectly via the promotion of endothelial cell integrity and nitric oxide (NO) function (6–14). Additional protective effects of estrogen may be due to native antioxidant properties of the hormone (15). In this chapter, vasoprotective actions of estrogen exerted at the level of the arterial wall will be considered in the context of balloon injury models and hypercholesterolemia.